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Chemical Structure| 520-26-3 Chemical Structure| 520-26-3
Chemical Structure| 520-26-3

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Hesperidin is a flavanone glycoside which can be extracted in citrus fruits.

Synonyms: Hesperetin 7-rutinoside; Cirantin; USAF CF-3

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Product Details of Hesperidin

CAS No. :520-26-3
Formula : C28H34O15
M.W : 610.56
SMILES Code : O=C1C2=C(C=C(C=C2O[C@@H](C1)C3=CC(O)=C(OC)C=C3)O[C@@H]4O[C@@H]([C@H]([C@@H]([C@H]4O)O)O)CO[C@@H]5O[C@@H](C)[C@@H]([C@H]([C@H]5O)O)O)O
Synonyms :
Hesperetin 7-rutinoside; Cirantin; USAF CF-3
MDL No. :MFCD00075663
InChI Key :QUQPHWDTPGMPEX-QJBIFVCTSA-N
Pubchem ID :10621

Safety of Hesperidin

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of Hesperidin

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 520-26-3 ]

[ 520-26-3 ] Synthesis Path-Downstream   1~54

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  • (Ξ)-5-hydroxy-2-(4-methoxy-3-propoxycarbonyloxy-phenyl)-7-(<i>O</i>6-α-L-rhamnopyranosyl-β-D-glucopyranosyloxy)-chroman-4-one [ No CAS ]
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YieldReaction ConditionsOperation in experiment
85.7% With morpholine; iodine; at 40 - 70℃;Large scale; Green chemistry; In 20L reaction kettle, add hesperidin 2 kg, iodine 0.92 kg, then add morpholine 12L. Start stirring and elevating temperature. When the temperature rises to 40 deg.C, sample is completely dissolved, At 45 deg.C ± 5 deg.C maintain temperature for 0.5 hours.Then, increase the temperature to 70 deg.C ± 5 deg.C and maintain the temperature and stir for 1.5-3 hours (HPLC monitoring hesperdin completely after transformation as the end point of the reaction). Recovery solvent to reactant into a viscous, adding 12L purified water, stirring, the material after being homogenized, the hydraulic the reaction buffer tank, adding hydrochloric acid adjusting pH=5-7 to crystallization, filtration, filter cake and filtrate, the filtrate pH=2 adjusted by adding hydrochloric acid, slowly adding 30% hydrogen peroxide 0.41 kg, filter, recovery elemental iodine. The filter cake is washed with a large amount of water washing, diosmin mode crude product obtained. Dissolving the purified water is added to the purification tank 12L and 0.39 kg sodium hydroxide, stir until completely dissolved after diosmin mode crude product into the continue to stir until completely dissolved, slowly adding at 20L acetonitrile, the solid is separated out, filtering, takes filters cake (diosmin mode sodium salt purity is of 99.27%), again dissolving the purified water is added to the purification tank 30L, then add and stir the filter cake to be completely dissolved, slowly dilute hydrochloric acid in this case adjusting pH=5-7, a large number of solid precipitation, filtration, the filter cake is washed with a large amount of purified water washing 1 hours, collecting filter cake, is put into the 80 C ± 5 C blast drying, crushing, diosmin mode the finished product to 1.69 kg, the purity is 99.44%, the yield is 85.7%, to the solvent recovery rate 80.1%, iodine recovery rate 89.6%, residual solvent, -related impurities are standard.
With pyridine; iodine; sodium hydroxide; at 95 - 105℃;Product distribution / selectivity; 100 gm of hesperidin , 700 ml of recovered pyridine, 9.8 gm of sodium hydroxide and 45.6 gm of iodine were charged in 2 liter clean glass assembly . The resulting solution was heated to 95-1050C for 9 - 10 hrs. Reaction was monitored by HPLC. Pyridine was recovered completely by distillation. Charged methanol to the resulting solid, the reaction mass was heated to reflux and filtered at room temperature. The solid obtained was treated with sodium thiosulfate solution and 900 ml, 5% aqueous NaOH solution. pH 2-4 was adjusted with cone, sulfuric acid. Reaction mass was filtered to obtain crude diosmin. Crude diosmin obtained was 80 - 86 gm. Purity was 98.6 %.
13.1 g Take an amount of 95% hesperidin 20g (previously 90 dried 3-4h), DMSO50ml dissolved by heating, the other to take 3gKBH4, graded by adding, to the reduction of hesperidin naringin type flavan-4- alcohol completely (approximately overnight , UV monitor, under alkaline conditions scans at no absorption peak at 360nm).Slowly adding 5ml of concentrated sulfuric acid (2ml particularly slow first, the solution became light red), mix well (solution becomes light red) was added slowly added anhydrous n-amyl alcohol 120ml, precipitation sink to the bottom, still 30min, poured out positive amyl alcohol solution was added to the precipitate in anhydrous n-amyl alcohol 20ml, stirring rapidly pinching solution, n-amyl alcohol was decanted, treated twice with the law, anhydrous pyridine 40ml, by adding iodine 8.3g, and stir until dissolved, no calcium sulfate 5g, stir, sealed in a water bath at 55 96h after continuous reaction.Activated carbon was added 5.0, add water 500ml, stirring slowly adding phosphoric acid modulation pH5, filtration, the filtrate was adsorbed by 300gD101 macroporous resin, 500ml water to remove pyridine, iodine ions and other impurities, and then 0.1% 0.5% phosphoric acid vitamin C400ml further elution remove residual iodine, pyridine and other impurities, washed with water 300ml, 2000ml eluted with 60% ethanol, recovering ethanol under reduced pressure.After recovery of ethanol was combined with activated charcoal 2g, mixing, filtration, water was recovered under reduced pressure to dryness to obtain Diosmetinidin-7-O-rutinoside, orange powder 13.1 g.
93 kg With bromine; iodine; In N,N-dimethyl-formamide; at 90 - 120℃;Large scale; in a 500kg of reactor, added 300.0kg of DMF, slowly added 100. 0kg of hesperidin, then added iodine1.0~5.0kg and bromine 1.0~3.0kg, while stirring the reaction was slowly heated to 90~120 C and at this temperature keep the reaction for 12~16h. The content of diosmin was detected by the sample. When the content of hesperidin was less than 1.0% then stop the reaction. Filtration, the filtrate at 80 ~ 95 C and under the vacuum is - (0.05 ~ .07) Mpa carried out recovery of solvent, to obtain creamy diosmin . in the paste creamy diosmin added 1200kg of purified water, stirred properly , stir, heated up to 40 ~ 70 C and maintain this temperature for 30 ~ 60min, Pressure filtration and wash until the outflow of water is clear. The filter cake dried in the drying room to moisture 8 ~ 15% to obtain crude product 108kg. The crude product was put into the reactor, added 864kg, 648kg and 432kg of 85% ethanol respectively, and then adding 400kg of iodine removing agent, stirring and refluxing for 60min, 40min and 30min respectively. Pressure filtration and wash until the outflow of water is clear. The filter cake was put into a reaction kettle, 700 kg of purified water, stirred properly until became thin paste, with hydrochloric acid, sulfuric acid or acetic acid PH as adjusted to 5, boiled for 40min, Pressure filtration, washing to the outflow of water until was neutral, filter cake was flash Dried to obtain 93 kg of the dried product, then granulated with a micropowder machine to obtain the diosmin according to EU EP 8.0.
With pyridine; iodine; at 100℃; for 12h;Large scale; 300 kg of liquid phase content of 95%New hesperidin, 1800 kg pyridine, 240 kg iodine into 3000 litersIn the kettle, the temperature is raised to 100 C for 12 hours, the liquid phase monitors the new hesperidin content to less than 2%, and the pyridine is recovered under reduced pressure to no liquid.After the body is steamed, the new odisamine is obtained

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  • (3,5-diacetoxy-phenyl)-[<i>O</i>2,<i>O</i>3,<i>O</i>4-triacetyl-<i>O</i>6-(tri-<i>O</i>-acetyl-α-L-rhamnopyranosyl)-β-D-glucopyranoside [ No CAS ]
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  • C40H54O25 [ No CAS ]
  • C46H64O30 [ No CAS ]
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  • hesperetin [ No CAS ]
  • hexa-<i>O</i>-acetyl-α-rutinosyl bromide [ No CAS ]
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  • chlorocarbonoic acid methyl ester [ No CAS ]
  • (Ξ)-5-hydroxy-2-(4-methoxy-3-methoxycarbonyloxy-phenyl)-7-(<i>O</i>6-α-L-rhamnopyranosyl-β-D-glucopyranosyloxy)-chroman-4-one [ No CAS ]
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  • hesperetin 7‐O‐β‐D‐glucopyranoside [ No CAS ]
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YieldReaction ConditionsOperation in experiment
L. acidophilus NCC 3010 crude extract; for 4 - 8h;pH 4 - 6;Enzymatic reaction;Product distribution / selectivity; Cleavage of <strong>[520-26-3]hesperidin</strong> by bacterial crude extracts in vitro To test if the bacterial alpha-rhamnosidases can recognise and cleave <strong>[520-26-3]hesperidin</strong> as a substrate, the crude extracts of the cells grown in the presence of rhamnose are incubated with <strong>[520-26-3]hesperidin</strong> at pH 4 and pH 6 for 4 hours and 8 hours and the analysis is done by HPLC. The results are presented in the table below as a percentage of <strong>[520-26-3]hesperidin</strong> or its derivatives based on the total <strong>[520-26-3]hesperidin</strong> amounts at the beginning of the reaction (0.08mg/mL). The tests were performed with 0.08 mg <strong>[520-26-3]hesperidin</strong>/mL, which is an approximate concentration of <strong>[520-26-3]hesperidin</strong> aimed for the final product and crude extracts of 3x109 bacteria/mL. The results show that the two strains have both alpha-rhamnosidase and beta-glucosidase activity and as a consequence cleave <strong>[520-26-3]hesperidin</strong> into hesperetin-7-glucoside and aglycone to different extents, depending on the reaction conditions. The results suggest that bacteria can be used for partial <strong>[520-26-3]hesperidin</strong> transformation into hesperetin-7-glucoside and aglycone in situ.
L. plantarum NCC 1313 crude extract; for 4 - 8h;pH 4 - 6;Enzymatic reaction;Product distribution / selectivity; Cleavage of <strong>[520-26-3]hesperidin</strong> by bacterial crude extracts in vitro To test if the bacterial alpha-rhamnosidases can recognise and cleave <strong>[520-26-3]hesperidin</strong> as a substrate, the crude extracts of the cells grown in the presence of rhamnose are incubated with <strong>[520-26-3]hesperidin</strong> at pH 4 and pH 6 for 4 hours and 8 hours and the analysis is done by HPLC. The results are presented in the table below as a percentage of <strong>[520-26-3]hesperidin</strong> or its derivatives based on the total <strong>[520-26-3]hesperidin</strong> amounts at the beginning of the reaction (0.08mg/mL). The tests were performed with 0.08 mg <strong>[520-26-3]hesperidin</strong>/mL, which is an approximate concentration of <strong>[520-26-3]hesperidin</strong> aimed for the final product and crude extracts of 3x109 bacteria/mL. The results show that the two strains have both alpha-rhamnosidase and beta-glucosidase activity and as a consequence cleave <strong>[520-26-3]hesperidin</strong> into hesperetin-7-glucoside and aglycone to different extents, depending on the reaction conditions. The results suggest that bacteria can be used for partial <strong>[520-26-3]hesperidin</strong> transformation into hesperetin-7-glucoside and aglycone in situ.
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YieldReaction ConditionsOperation in experiment
In ethanol; at 20℃; for 0.333333h;pH 7.4;in a dark; Tris-HCl buffer;Reactivity; The antioxidative activity in a hydrophilic solvent was measured for <strong>[520-26-3]hesperidin</strong> (HE) and the isolated 8-hydroxyhesperetin (8OH-HE) It should be noted that antioxidative activity was measured in accordance with the radical scavenging ability measurement method described in Yamaguchi, et al., Biosci. Biotechnol. Biochem., 62, 1201-1204, 1998. More specifically, an 8OH-HE sample solution and HE sample solution were first prepared having concentrations of 0.1 muM, 1 muM and 10 muM by dissolving 8OH-HE or HE in ethanol.. 200 muL of each sample solution was then mixed into 800 muL of 0.1 M Tris-HCl buffer (pH 7.4). lml of 500muM DPPH (1,1-diphenyl-2-picrylhydrazyl) in ethanol was added to each mixture to prepare reaction solutions. After adequately mixing the reaction solutions, they were allowed to react for 20 minutes in a dark location at room temperature. Next, 20 muL of each reaction solution was injected into an analytical HPLC system (LC-10A) using a microsyringe to analyze the DPPH concentration. The DPPH concentration was calculated from peak area of DPPH. It should be noted that a column having an inner diameter of 4.6 mm and length of 150 mm (TSKgel Octyl-80TS, produced by YMC) was used in HPLC analysis, the elution solvent consisted of a 30:70 ratio of distilled water and methanol, the flow rate was 1 mL/minute and the detection wavelength was 517 nm. Using 200 muL of a solution of ethanol only instead of the sample solutions for the control, the peak area of DPPH was similarly measured for the control by HPLC analysis. The radical scavenging activity (%) of 8OH-HE and HE were then determined according to the calculation formula indicated in Formula 1.Radical scavenging activity= 100 - DPPH peak area of sample DPPH peak area of control× 100 Furthermore, the higher value for radical scavenging activity, the higher the antioxidative activity. The results are shown in Fig. 1. The 8OH-HE formed from HE by fermentation treatment was determined to demonstrate a much higher level of antioxidative activity than HE in the hydrophilic solvent.
YieldReaction ConditionsOperation in experiment
B. The slurry was cooled to 40 C. with continued stirring, filtered, and the residue washed with warm H2 O (1 * 1 l.), isopropanol (1 * 0.5 l.), and dried in vacuo (50 C.) to afford 62.6 g of fluffy white hesperidin.
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  • concentrated H2 SO4 [ No CAS ]
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YieldReaction ConditionsOperation in experiment
In methanol; water; B. <strong>[520-26-3]Hesperidin</strong> (10 kg) is charged to the 500 liter stirred reactor under nitrogen along with 150 liters of absolute methanol and 10 kg of concentrated H2 SO4. The mixture is stirred at reflux for 5 hours. Then, 50 liters of methanol are taken off overhead over 3 hours. The 100 liters of product is then gradually fed over 2 hours to 400 liters of vigorously stirred boiling 95-100 C. water under nitrogen. The hesperetin precipitates. The water is cooled and the solid hesperetin is recovered in 85+% yield from the water by filtration. After water rinsing thrice, the hesperetin is dried. Analysis indicates that it is 97%+ pure.
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YieldReaction ConditionsOperation in experiment
87% With sulfuric acid; In ethanol; for 8h;Reflux; Weigh <strong>[520-26-3]hesperidin</strong> (72g, about 0.12mol) into a 1000mL round-bottomed flask, add 720mL of 10% concentrated sulfuric acid ethanol solution, place in an oil bath and stir well, and heat to reflux. After 8 hours of reaction, after cooling, pour Into ice water, a solid precipitated, left to stand, suction filtered, and dried.The crude product was heated and dissolved with ethanol, and the activated carbon was decolorized and filtered.The filtrate was recovered under reduced pressure. The solid was recrystallized from ethanol and dichloromethane.A white solid was precipitated, suction filtered, and dried to obtain a hesperetin powder (31.5 g) in a yield of 87%.
87% With sulfuric acid; In ethanol; at 80℃; for 8h; To a solution of ethanol (640 mL) and 98% H2SO4 (80 mL) was added <strong>[520-26-3]hesperidin</strong> (72 g, 0.12 mol),the suspension was heated at 80 C for 8 h. The reaction mixture was allowed to cool to roomtemperature, then poured into ice water (2 L). The precipitate was filtered, washed with water anddried. The mixture was dissolved in ethanol and heated to reflux for 1 h, heating was stopped andactivated charcoal was added to the solution for 15 min. The solution was filtered and washed withhot ethanol. The ethanol solution was concentrated under the reduced pressure, and the residue wasrecrystallized from ethanol and CH2Cl2 to obtain hesperetin (1) [23] as a white powder (31.5 g, yield87%), m.p. 229.5-231.6 C; 1H-NMR: delta 12.14 (s, 1H, 5-OH), 10.80 (s, 1H, 7-OH), 9.11 (s, 1H, 3?-OH),6.95-6.92 (m, J = 5.1, 3.2 Hz, 2H, 2?-H, 5?-H), 6.87 (dd, J = 8.3, 2.0 Hz, 1H, 6?-H), 5.89 (d, J = 2.1 Hz,1H, 8-H), 5.88 (d, J = 2.1 Hz, 1H, 6-H), 5.43 (dd, J = 12.4, 3.0 Hz, 1H, 2-H), 3.77 (s, 3H, OCH3), 3.20(dd, J = 17.1, 12.4 Hz, 1H, 3-H), 2.70 (dd, J = 17.1, 3.1 Hz, 1H, 3-H). 13C-NMR:delta 196.61, 167.22, 163.92,163.24, 148.34, 146.85, 131.54, 118.20, 114.45, 112.34, 102.21, 96.31, 95.49, 78.68, 56.07, 42.46. HRMS (ESI):Calcd. C16H14O6, [M + H]+ m/z: 303.0875, found: 303.0881.
65.4% With sulfuric acid; In methanol; at 60℃; for 7.5h; General procedure: Compound 2 was synthesized by literature procedure.1 A mixture of 1 (3.5 g, 5.7 mmol) and H2SO4 (10 mL) in anhydrous CH3OH (280 mL) was stirred at 60C for 7.5 h, ethyl acetate (1.2 L) was then added at 20C . The solution was washed with H2O (420 mL), and dried (Na2SO4). Evaporation afforded pale-yellow powder. The crude product was dissolved in acetone (70 mL) and added dropwise (60 min) to a stirred mixture of H2O/acetic acid (150:1, 700 mL) at 95C . The slurry was cooled to 45C and the product filtered and dried in vacuo.
52.1% With sulfuric acid; In ethanol; for 7.5h;Reflux; <strong>[520-26-3]Hesperidin</strong> 1.50 g (2.46 mmol) was added to 90 mL of absolute ethanol and 3 mL of concentrated sulfuric acid was added with vigorous stirring. The mixture was heated under reflux for 7.5 h.The reaction mixture was distilled off under reduced pressure. Most of the ethanol was distilled off under reduced pressure. The residue was poured into distilled water and extracted with ethyl acetate (3 x 90 mL). The extracts were combined and washed with distilled water until neutral. Ethyl acetate was distilled off, A yellow residue was obtained, and the crude product was recrystallized from ethanol / water.The yield was 52.1%,
49% With sulfuric acid; water; at 20℃; for 0.166667h; General procedure: Sulfuric acid (2.0mL, 0.037mmol) was added dropwise to a beaker (100 mL) containing scutellarin (50 mg, 0.11 mmol). It was shaken or agitated by ultrasound agitated to dissolve the substrate in the acid at room temperature. Water (2.0 mL) was then added carefully dropwise. When the evolution of heat ceased (in 10 minutes), the mixture was added to water (15 mL) in one portion with stirring with a glass rod. The yellow crystals that were deposited were collected by suction filtration and washed by water (5 mL). In most cases, such products were pure enough for direct use. Moreover, it could be further purified by recrystallisation from aqueous methanol (70%, v/v) or column chromatography on silica gel (eluent:ethyl acetate/formic acid/water=100/4/3, v/v/v, Rfs of SCU and SCUE were 0.1 and 0.8 on silica gel GF254 respectively). Light yellow crystals were obtained after recrystallisation (28.5mg, 93% yield); m.p. 285-287C (>300C)27. IR (KBr, cm-1): numax 3442, 3331, 3098, 1671, 1619, 1587, 1509. 1H NMR (500MHz, DMSO-d6): delta 12.80 (s, 1H, 5-OH), 10.48 (s, 1H, 7-OH), 10.33 (s, 1H, 4?-OH), 8.75 (s, 1H, 6-OH), 7.92 (d, 2H, J=8.6Hz, C2?, C6?-H), 6.92 (d, 2H, J=8.6Hz, C3?, C5?-H), 6.75 (s, 1H, C3-H), 6.58 (s, 1H, C8-H). HR-ESI-MS (m/z): 309.0363 for [M+Na]+, calcd 309.0370.
To a solution of methanol (280mL) and 96% H2SO4 (10mL) was added <strong>[520-26-3]hesperidin</strong> 1 (3.5g, 5.73mmol), the suspension was heated at 70C for 8h. The reaction mixture was allowed to cool to room temperature, then put into EtOAc (50mL). The organic phase was washed with water (3×400mL), then concentrated in vacuo. The residue dissolved in acetone (70mL) was dropped to a hot 1% AcOH aqueous solution (700mL), the mixture was stirred at 70C for 1.5h, cooled, filtrated and dried. Hesperitin was obtained, mp: 230-232C. 1H NMR (600MHz, DMSO-d6): delta 10.16 (br s, 1H, OH), 8.03 (br s, 1H, OH), 7.47 (m, 1H, OH), 6.87-7.01 (m, 3H, ArH), 5.98 (s, 1H, ArH), 5.29 (dd, J=12.8, 2.9Hz, 1H, H-2), 3.89 (s, 3H, O-CH3), 3.05 (dd, J=17.1, 12.9Hz, 1H, cis-H-3), 2.73 (dd, J=17.1, 3.0Hz, 1H, trans-H-3).
0.13 mol With sulfuric acid; In dimethyl sulfoxide; at 100℃; for 2h;pH 5; 0.16mol <strong>[520-26-3]hesperidin</strong> placed in the reaction vessel,Addition of 500 mL of DMSO gave a hydrolyzate.Then dropping 50mL concentrated sulfuric acid to adjust the pH of the hydrolyzate is 5,The reaction was further stirred at 100 C for 2 hours under magnetic stirring,Standing filtered to give a precipitate,Drying to obtain 0.13mol hesperetin.

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  • [ 14265-53-3 ]
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  • [ 520-26-3 ]
  • hesperidin 2'',2''',3'',3''',4'',4'''-O-hexasulfate [ No CAS ]
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  • [ 520-26-3 ]
  • hesperetin 3',7-O-disulfate [ No CAS ]
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  • [ 67-56-1 ]
  • [ 520-26-3 ]
  • [ 184239-14-3 ]
  • [ 520-33-2 ]
 

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